This project focuses on: (1) describing the characteristic losses in muscle strength, muscle mass, and physical functioning that occur with aging by examining the entire adult lifespan and (2) evaluating the impact of such loss on function and longevity. We previously demonstrated that declining muscle strength and rate of change in muscle strength independently contribute to mortality in men when considering age, physical activity and muscle mass. Further, strength was directly related to walking speed a risk indicator for disability in the elderly. We have further shown that muscle power and movement speed independently contribute to longevity. Recently, we participated in an international collaborative study which conducted a quantitative systematic review and meta-analysis, examining the associations between physical capability (grip strength, walking speed, chair rising and standing balance times) and mortality in community-dwelling populations. Evidence was found for associations between poorer performance capability and increased mortality. A key contributor to maintenance and utilization of muscle is the nervous system. Previously, we have shown that peripheral nerve function impacted muscle strength and power independent of body size and activity levels. Further observations suggest that force generation requires greater nervous system activity to obtain a given force level as we age to compensate for decreased strength, decline in movement speed and response times. Alterations in both the peripheral and central nervous systems seem to be major contributors to the sarcopenic process. In related work, we found decline in vibrotactile sensitivity in the feet with age, and that vibrotactile sensitivity is directly related to physical performance with slower self-selected normal gait speed. Thus both sensory and motor components of the peripheral nervous system seem associated with a decline in mobility which subsequently contributes to loss of leg strength and corresponding muscle changes. Based on these observations, we developed a Cumulative Somatosensory Impairment Index (CSII) that detects group differences in lower limb somatosensory impairment and independently predicts decline in postural control over 3 years. Such an index may prove useful in assessing future physical functioning problems. When considering sensorimotor and psychosocial factors in relationship to adaptive walking tasks in older adults, we found that poor knee extensor strength was associated with an inability to perform tasks demanding an increase in walking speed (fast walking and obstacle crossing). Both poor lower limb coordination and higher CSII were significantly associated with failure in tests that demanded precise control over foot placement (obstacle crossing and narrow-based walking). In contrast, poor cognition was associated with an inability to perform walking while talking. Poor personal mastery was the only variable associated with failure in all walking tests. The impact of sarcopenia on mortality may in part depend on homeostatic factors required for efficient neuromuscular function. Recently, we studied the relationship of glucose intolerance with changes in muscle mass with aging. Associated with the metabolic changes, we found that weight loss, frequently seen prior to death, often begins 9 or more years before death. This effect is likely related to differences in dietary intake and energy metabolism during these years prior to death. Age-related declines in testosterone in men may contribute to losses in muscle strength and physical performance. Using data on older men from the InCHIANTI study we found that severity of hypogonadal status was associated with less favorable hemoglobin levels, hand grip strength and physical performance score but not with calf muscle mass or walking speed. Another area of interest has been the importance of physical actiivity and exercise for maintaining strength and muscle mass. We have observed that both being physically active and maintaining higher intensity activity over time is associated with lower mortality in men, but not women. In women, overall activity, including low and moderate levels, are equally important. In addition, in the elderly, activity restriction can occur because of fear of falling. We observed that such fears adversely affect physical function and autonomy in the InChianti population. Thus both psychological and physical factors appear to contribute to fear of falling and the associated restrictions in physical activity. Furthermore, differences in physical and psychosocial characteristics exist between older persons who have fear of falling in community environment activities and those who express fear of falling in home environment activities. Personality, a significant determinant of health behaviors including physical activity, could therefore impact muscle strength throughout adulthood and affect the rate of muscle strength decline with aging. Personality typologies combining high neuroticism, low extraversion and low conscientiousness have been associated with multiple risky health behaviors which raise the question whether there is an association between individual and combined typologies consisting of high N, low E, and low C and muscle strength. Using Baltimore Longitudinal Study of Aging data, high N, particularly when combined with either low E or low C, was associated with lower muscle strength compared with having only one or none of these personality types. Physical activity level appears to partly explain some of the associations. Some aspects of personality appear to contribute to age-associated strength loss and may need to be considered in developing approaches to overcome these losses. Work in this project will continue to explore important physiological, social and activity related factors contributing to strength loss and performance declines with aging. The long term goal is to develop strategies that can be used across the adult lifespan to maintain and improve physical performance.